Camptothecin analogues, such as topotecan, have been shown to be useful as both antineoplastic and antiviral therapeutic agents. A process for the total synthesis of racemic topotecan, a camptothecin analogue, is described in copending U.S. Ser. No. 07/941,496 now abandoned. A recent example of a different total synthesis was published by Comins, et al., J. Am. Chem. Soc., 114, 10971, 1992. As is often the case, optimal therapeutic activity is provided by only one configuration of the molecule. It is therefore desirable to produce this material in a form which is highly enriched in only one absolute configuration of the chiral center.
A. I. Meyers et al., J. Org. Chem., 38, 1973, 1974 describes the synthesis of racemic camptothecin analogues by the coupling of a carboxylic acid with a pyrrolo[3,4-b]quinoline. However, that process lacks the desirable ability to introduce chirality into the target camptothecin analogue.